Phase I study of the pharmacokinetics and safety of single and multiple doses of intravenous N-acetylcysteine in healthy Chinese subjects

J. Sun, X. Zhang, L. Wang, A.F.D. Di Stefano, V. Zanin, P. Magrone, Y. Yuan

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. yyz28@medmail.com.cn

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• Pharmacology

OBJECTIVE: The aim of the study was to determine the pharmacokinetics (PK) and safety of single and repeat doses of intravenous (IV) N-acetylcysteine (NAC) in Chinese subjects.

PATIENTS AND METHODS: A total of 24 healthy male and female Chinese subjects aged 19-40 years were enrolled in this open-label phase I study. All subjects received a single dose of NAC 600 mg IV on day 1 and, after a 3-day washout, received repeat doses of NAC 600 mg IV (twice daily on days 4 and 5 and once on day 6).

RESULTS: Following a single dose, plasma NAC concentrations peaked rapidly, starting to fall at the end of the 5-minute infusion in a multiphasic manner. Mean Cmax was 83.30 μg/mL (CV% 30.7%), median Tmax was 0.083 h (range 0.08-0.25 h), and mean AUC(0-12 h) was 81.87 h*μg/mL (CV 14.0%). Following repeat dosing, Cmax was approximately 20% higher than after a single dose, with similar Tmax. Total exposure AUC(0-12) was 13% higher at steady state than after single dosing. The accumulation ratio was approximately 1.13, indicating only a slight accumulation with multiple dosing. NAC was eliminated with T1/2 of approximately 8 hours. Around 15% of the total NAC dose was excreted in the urine in the 32 hours post-dose, keeping with extensive NAC metabolism and transformation. Renal clearance of NAC was 995.2 mL/h (CV 50.2%). IV NAC was well tolerated after both single and multiple dosing.

CONCLUSIONS: This is the first robust study evaluating the PK and safety of IV NAC 600 mg in Chinese subjects and provides important data if this agent is to be used IV as a mucolytic in this population.

This article has been corrected on June 28, 2024. Erratum notice in: Eur Rev Med Pharmacol Sci 2024; 28 (12): 3806-3806.

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